Significant Contributions in National and International Research

The focus of Dr. Misra’s research has been on obesity, metabolic syndrome (syndrome
X), diabetes mellitus, hyperlipidemia and other cardiovascular risk factors in Asian
Indians and rare disorders of adipose tissue.

Obesity, Diabetes, Insulin Resistance, and Cardiovascular Risk in the Underprivileged
Population in India: Epidemiological Studies

For the first time, Dr. Misra’s team showed a high prevalence of Type 2 Diabetes
Mellitus, abdominal obesity, dyslipidemia and metabolic syndrome in the underprivileged
population living in urban resettlement colonies of New Delhi. Other previously
unreported observations on the same population included a high prevalence of hyperhomocysteinemia,
endothelial dysfunction and subclinical inflammation. His team also carried out
epidemiological study of metabolic syndrome and cardiovascular risk factors of post-menopausal
women belonging to low socio-economic stratum, and reported a marked clustering
of cardiovascular risk factors. His team’s health awareness program in poor socio-economic
stratum is based on the above findings.

Dr. Misra and his team have reported markedly imbalanced nutrition among the underprivileged;
high total and saturated fat, low intakes of fibre and ω-3 fatty acids, and low
intakes of anti-oxidants in the people belonging to low socio-economic stratum in
urban slums.

In serial studies, Dr. Misra and his team recorded a rising prevalence of obesity
among schoolchildren in Delhi. They have also reported a high intake of energy-dense
food and carbonated beverages in children, resulting in a high prevalence of insulin
resistance among them, which correlates to the intake of n-6 fatty acids. Other
important findings include a high intake of saturated fat and trans fatty acids.

Based on high levels of C-reactive protein in children, Dr. Misra calculated that
saturated fat intake in adolescents should be restricted to <7%. In a preliminary
communication, they reported that ~ 65% of adolescent and young population in schools
and colleges of New Delhi are sedentary.

Determinants of Diabetes and Cardiovascular Risk Factors in Asian Indians: A Multi-Site
Epidemiological Study in USA and Urban and Rural Populations Residing in India in
Collaboration With Texas A&M University, USA:

This important study, carried out for the first time, aimed to assess the obesity,
insulin resistance, diabetes, and other cardiovascular risk factors in Asian Indians
at three sites: USA, urban and rural India. The study shows a stepwise increase
in the prevalence of diabetes and cardiovascular risk factors in rural and urban
populations in India, and migrant Asian Indians at 6 sites in USA. The study also
highlights the high prevalence of abdominal obesity and metabolic syndrome in Asian
Indians. An important finding is the rising prevalence of diabetes and obesity in
rural populations as well.

High Prevalence of Diabetes, Other Cardiovascular Risk Factors and Imbalanced Nutrition
in Women: A Country wide, Multi-site Study

This study, done on four urban and four rural centers in India, shows high prevalence
of diabetes, hypertension, obesity and dyslipidemia in women >35 years of age, in
addition of highly imbalanced dietary profile.

Dr. Misra and his team studied hepatic gluconeogenesis metabolism in non-diabetic
Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo
(31P) phosphorous magnetic resonance spectroscopy (MRS). In this novel experiment,
they observed derangements in hepatic gluconeogenesis in obese and non-obese Asian
Indians with NAFLD.

This is a very important study. It shows that people with fatty liver are pre-disposed
to develop diabetes. Further, this in vivo method holds promise as a non-invasive
method for the prediction of diabetes.

A New Laboratory Measure for the Assessment of Long-Term Glycemia in Diabetes Mellitus:

In collaboration with Indian Institute of Technology, New Delhi, Dr. Misra and his
team investigated intrinsic fluorescence property of hemoglobin-AGE as a simple,
accurate and cost-effective method for the assessment of glycemic status and as
an alternative to the current standard investigation of glycosylated hemoglobin.
Experimental observations in male Wistar rats and human beings indicate that hemoglobin-AGE
is an efficient fluorescence based biosensing molecule for the long-term monitoring
of glycemic control in diabetes. These are hitherto unreported observations and
provide a novel laboratory tool for the monitoring of diabetes mellitus.

Currently, as part of a new study, he and his team are testing Hb-AGE as a method
for monitoring of glycemia in patients with diabetes mellitus.

Lipodystrophies are rare disorders of adipose tissue. Investigations on this rare
disorder may answer some complex questions pertaining to the pathogenesis of insulin
resistance, diabetes and fatty liver. Dr. Misra has worked extensively on the clinical
and pathophysiological correlates of Acquired Generalized Lipodystrophy and devised
the classification and diagnostic criteria of these disorders; as also that an extensive
study on Acquired Partial Lipodystrophy (Barraquer Simons Syndrome) leads to new
diagnostic criteria and classification. He has also done research on Familial Partial
Lipodystrophy, Dunnigan Variety, and lipodystrophy in HIV-infected patients.

Central nervous system has been rarely researched in patients with diabetes. For
the first time, Dr. Misra and his team reported cognitive dysfunctions in young
patients with type 2 diabetes, and further showed the relation of central neuropathy
with NAT polymorphisms in Asian Indian patients. They have further shown cognitive
and neuronal dysfunction in young patients with hypertension, hyperlipidemia etc.

In a recent investigation, they have investigated cognitive dysfunction, and cerebral
blood flow using positron emission tomography scan and cerebral neuronal functions
using proton magnetic resonance spectroscopy in young Asian Indian patients with
hyperlipidemia. Importantly, these young patients have abnormal cerebral functions.

This is the first study showing the usefulness of resistance muscle exercise in
patients of diabetes. Not only resistance exercise (using small weights) improves
blood glucose profile but also decreases subcutaneous fat, which does not decrease
in a selective manner to any weight loss therapy. Based on this study, Dr. Misra
and his team have proposed that the resistance should be included in the exercise
advisory of Asian Indians with diabetes.

In this study, new phenotypic markers (‘buffalo hump’ and ‘double chin’) for the
prediction of metabolic syndrome has been investigated in Asian Indians for the
first time in the world. The identification of these phenotypic markers in a person
means that he/she is at a high risk for development of metabolic syndrome and diabetes.
These simple physical signs could be used by any physician anywhere in India to
identify those at risk of diabetes. This is a simple yet very useful research paper.

Simvastatin as a Novel Treatment for Non-Significant Macular Edema in Patients with
Type 2 Diabetes

Though hyperlipidemia has been correlated to the occurrence of diabetic retinopathy,
specifically hard exudates, no intervention study with lipid-lowering treatment
was available. Dr. Misra and his team were the first to show that simvastatin use
retards clinically significant macular edema in diabetic patients in a randomized
double-blind controlled trial.

Metabolic and Genetic Investigations of Obstructive Sleep Apnea

Obstructive sleep apnoea (OSA) may be a risk factor for hypertension, diabetes and
cardiovascular disease. For the first time, Dr. Misra and his team reported increased
serum levels of TNF- in obese Asian Indians showing a strong association with OSA,
and significant association of OSA with -308G/A promoter polymorphism of TNF- gene.
Further, they also reported the association of PPAR (Pro12Ala) and Neuropeptide-Y
(Leu7Pro) gene polymorphisms in OSA for the first time.

In a case controlled study, Dr. Misra and his team have demonstrated that people
with fatty liver have a high predisposition to develop metabolic syndrome and diabetes.

In another randomized controlled trial, patients with fatty liver are being treated
with MUFAs-rich oils. This a preliminary study to see dietary treatment to decrease
hepatic triglycerides.

Assessment of Trans Fatty Acid (TFA) Contents of Indian Foods:

This proposal aims to assess the TFA content of commonly consumed fast foods by
Urban Indians. It is also proposed to investigate the TFA content and the effect
of frying temperatures and time on the quality of edible oils. Using these TFA values
the study also proposes to assess the TFA consumption among different groups of
population and to correlate it with the anthropometric measurements. The proposal
also deals with identifying appropriate alternatives for reuse of degraded oils
after mild treatment at home or commercial outlets and to formulate a strategy to
limit/avoid TFA intake and to educate mothers/homemakers about the adverse effects
of TFA.